Developing climate-smart agriculture is an urgent necessity to ensure the food security of a growing global population, to improve the adaptation of agricultural systems to climatic hazards, and to reach a negative carbon balance. Different approaches are being explored to achieve those objectives, including the development of new technologies for efficiency improvements to current systems and substitution of chemical inputs by bio-inputs, but the urgency of the climatic, social, and environmental context calls for more disruptive actions to be taken. We propose an approach to the design of climate-smart production systems structured in four steps: (1) diagnosis of the study region on the basis of the three pillars of climate-smart agriculture, (2) co-design of a disruptive system only based on agroecological and bioeconomic principles, (3) long-term experimentation of this system, and (4) in itinere adjustment of the system based on collected data and on-field evaluations with agricultural stakeholders. The outcome of this approach is the agroecological microfarm named KARUSMART, settled in 2018 on one hectare in the North Basse-Terre region of Guadeloupe (F.W.I.). This study presents its co-design and experimentation stages as well as the first performance results. At the end of the first two years, this microfarm showed a clear improvement in 15 of the 19 indicators used to evaluate the performance of the actual farming systems in the study region. Among the most striking results are a clear superiority in nutritional performance from 3 pers.ha−1 to 8 pers.ha−1 and a reduction in GHG balance from +2.4 tCO2eq.ha−1 to −1.1 tCO2eq.ha−1 for the study area and the microfarm, respectively. These results are promising for developing climate-smart agricultural systems and need to be consolidated further through longer-term monitoring data, the implementation of more similar systems in the study area, and the implementation of the design principles in other contexts.